Download The Nucleic Acid Database: A Resource for

1095
Acta Cryst. (1998). D54, 1095±1104
The Nucleic Acid Database: A Resource for Nucleic Acid Science
Helen M. Berman,* Christine Zardecki and John Westbrook
NDB, Department of Chemistry, Rutgers University, 610 Taylor Road, Piscataway, NJ 08854-8087, USA.
E-mail: [email protected]
(Received 6 March 1998; accepted 4 June 1998 )
Abstract
The Nucleic Acid Database (NDB) distributes information about nucleic acid-containing structures. Here the
information content of the database as well as the query
capabilities are described. A summary of how the
technology developed by this project has been used to
develop other macromolecular databases is given.
1. Introduction
Nucleic acids have distinctive chemical and structural
features. There are 12 conformation angles which
describe the bonds interconnecting the base, sugars and
phosphates, and 16 different parameters which describe
the geometry of the base pairs. This potential conformational variability allows double-stranded DNA to be
¯exible enough to be coiled in the cell and for singlestranded RNA to fold into compact functional units.
Single-crystal nucleic acid crystallography began in the
1970's, almost 20 years after the discovery of the doublehelical form of DNA by Watson and Crick (Watson &
Crick, 1953). By 1990, there were more than 150 structures of DNA and RNA oligonucleotides, t-RNA, and a
handful of protein±nucleic acid complexes. The sample
set was thus large enough to begin to ask questions
about the effects of sequence and environment on the
structures of these biological molecules. The vision
behind the creation of the Nucleic Acid Database
(NDB; Berman et al., 1992) was to establish a resource
which enables researchers to easily answer these questions and to facilitate, in general, research about nucleic
acid structures. This resource would be realised through
the creation of a database of information about nucleic
acids which would have robust query capabilities. Thus,
not only would the users be able to extract coordinates
for a particular structure, but they would also be able to
select groups of structures based on particular characteristics and extract the experimental information and
derived features of these structures. In addition, it was
desired to be able to make correlations among different
characteristics of the structures so that eventually the
database would become a predictive tool.
At the time that the NDB was established, nucleic
acid structural information was found in both the
# 1998 International Union of Crystallography
Printed in Great Britain ± all rights reserved
Cambridge Structural Database (CSD; Allen et al.,
1979) and the Protein Data Bank (PDB; Bernstein et al.,
1977). Containing small nucleotides and dinucleoside
phosphates, the CSD had a very robust query engine but
it did not provide the specialized information required
to understand nucleic acid structures. The PDB
contained the larger oligonucleotides, but lacked a
query interface; although it now provides a browser, it is
not possible to extract derived data about groups of
structures. The original scope of the NDB project was to
create a `value-added' database containing structural
data for both RNA and DNA. The NDB is now the
direct deposition site for these structures and has
created a database with information about all nucleic
acid-containing crystals. The ways in which the NDB is
used to support research on nucleic acids are described
here. Additionally, we describe how we have applied the
technology developed by the NDB to other types of
macromolecular databases.
2. Information content of the NDB
In addition to coordinate data, the NDB contains
information about the experiments used to determine
the structures, including crystallization information,
data-collection information and re®nement statistics.
The database also stores derived information such as
valence geometry, torsion angles, base morphology
parameters and intermolecular contacts. Further annotation includes information about the overall structural
features. These include the conformational classes,
special structural features, biological functions, and
crystal packing classi®cations. Table 1 summarizes these
derived data and annotations. The organization of these
features into a database makes it possible to gain new
insights about structure using advanced techniques such
as data mining.
3. Validation procedures for nucleic acids
Structures are added to the database via two routes:
direct deposition (nucleic acids) and post processing of
PDB ®les (protein±nucleic acid complexes). All data are
transformed into mmCIF ®les which allows them to be
Acta Crystallographica Section D
ISSN 0907-4449 # 1998
1096
THE NUCLEIC ACID DATABASE
Table 1. Summary of derived data and annotations
(a) Annotations stored in the NDB
Structural features
NDB, PDB and CSD identi®ers
Availability of coordinates
Availability of structure factors
Sequence
Conformation type
Description of modi®ers of base, phosphate and sugar
Mismatched base-pairs
Name and binding type for drug
Description of base pairing
Description of asymmetric unit
Description of the biological unit
Crystal packing motif
(b) Derived data stored in the NDB
Covalent bond lengths and angles
Nonbonded contacts
Virtual bonds and angles involving P atoms
Backbone and side-chain torsion angles
Pseudorotation parameters
Base morphology parameters
Valence geometry r.m.s. deviations from small-molecule
standards
Sequence pattern statistics
checked automatically against the mmCIF dictionary
(Bourne et al., 1997). This creates a uniform archive to
ensure reliable query results. Structure checking is
accomplished using a suite of programs that verify
valence geometry, torsion angles, intermolecular
contacts and chirality. The dictionaries used for checking
the structures were developed from analyses of highresolution small-molecule structures from the CSD
(Clowney et al., 1996; Gelbin et al., 1996). The torsionangle ranges were analyzed from high-resolution nucleic
acid structures (Schneider et al., 1997). One important
outgrowth of this work was the creation of the force
constants and restraints that are now in common use for
crystallographic re®nement of nucleic acid structures
(Parkinson et al., 1996).
4. The characteristics and uses of the database
4.1. Basic features
The core of the NDB project (Fig. 1) is a relational database in which all of the primary and
derived data items are organized into tables. At
present there are over 90 tables in the NDB, with
each containing ®ve to 20 items. These tables contain
both experimental and derived information. Example
tables include: the citation table, which contains all
the items that are contained in literature references;
the cell_dimension table, which contains all items
related to crystal data; and the re®ne_parameters
table, which contains the items that describe the
re®nement statistics. Interaction with the database is
a two-step process (Fig. 2). In the ®rst step, the user
Fig. 1. Flow chart showing the
organization of the Nucleic Acid
Database project. The core of this
project is the database.
HELEN M. BERMAN, CHRISTINE ZARDECKI AND JOHN WESTBROOK
1097
Table 2. Examples of the Boolean logic used to construct an NDB query
Ê and R factor < 0.17 by authors A. Rich, R. E. Dickerson or O. Kennard.
Structure selection of B-DNAs with resolution 1.9 A
Table
Attribute (Item)
Operator
Operand
Logical
structure_summary
structure_summary
r_factor
r_factor
citation
Conformation_Type
Classi®cation
Upper_Resol_Limit
R_Value
Authors
=
=
<=
<
like
B
DNA
1.9
0.17
R.E.Dickerson
AND
AND
AND
AND
OR
structure_summary
structure_summary
r_factor
r_factor
citation
Conformation_Type
Classi®cation
Upper_Resol_Limit
R_Value
Authors
=
=
<=
<
like
B
DNA
1.9
0.17
A.Rich
AND
AND
AND
AND
OR
structure_summary
structure_summary
r_factor
r_factor
citation
Conformation_Type
Classi®cation
Upper_Resol_Limit
R_Value
Authors
=
=
<=
<
like
B
DNA
1.9
0.17
O.Kennard
AND
AND
AND
AND
de®nes the selection criteria by combining different
database items. As an example, one could select all
Ê,
B-DNA structures with resolution better than 2.0 A
R factor better than 0.17 and that they were determined
by Dickerson, Kennard or Rich. The logic for this
constraint is shown in Table 2.
Once the structures that meet the constraint criteria
have been selected, reports may be written using a
combination of table items. For any set of chosen
structures, a large variety of reports may be created. For
the example given above, a crystal data report or a
backbone torsion-angle report can be generated easily.
Or the user could write a report that lists the twist values
for all CG steps together with statistics, including mean,
median and range of values. The constraints used for the
reports do not have to be the same as those used to
select the structures.
The NDB can also be used to create graphical reports.
It is possible to produce pie charts, scattergrams and
histograms describing any aspect of a selected group of
structures. These capabilities were put to full use in
deriving the ranges of torsion angles for different types
of DNA helices (Schneider et al., 1997). Fig. 3 shows
some examples of the variety of reports one can make
about torsion angles.
Another very popular and useful report is the NDB
Atlas report page. Atlas pages are created directly from
the NDB database for a particular structure and contain
summary, crystallographic and experimental information about the structure, a molecular view of the biological unit and a crystal packing picture (Fig. 4). The
Atlas section of the NDB WWW site contains Atlas
entries for all of the structures in the database organized
by structure type.
4.2. Query capabilities
4.2.1. Character menu. The most direct access to the
database is through the use of SQL commands.
However, given that this is a specialist language, a
character menu has been constructed which allows
access to all of the tables in the database. Queries and
reports are constructed menu by menu. Both query
and report constraints can be saved in a `command'
®le which allows the user to access, revise and edit
these constraint and report de®nitions at any time.
These command ®les facilitate making multiple
reports about a particular set of structures quickly and
easily. This method is used to generate the summary
Fig. 2. Flow chart describing the steps
involved in using the NDB: structure selection and report generation.
1098
THE NUCLEIC ACID DATABASE
Table 3. Structure Finder Quick Reports
These prepared reports can be created for structures selected from the following databases using Structure Finder (http://ndbserver.rutgers.edu/)
Structure Finder database
Report name
Contains
NDB
NDB Status
Cell Dimensions
Primary Citation
Structure Identi®er
Sequence
NA Backbone Torsions
Processing status information
Crystallographic cell constants
Primary bibliographic citations
Identi®ers, descriptor, coordinate availability
Strand ID, sequence, strand length
Sugar±phosphate backbone torsion angles using NDB residue
numbering
Sugar±phosphate backbone torsion angles using PDB residue
numbering
Global base-pair parameters calculated using Curves 5.1
(Lavery & Sklenar, 1988)
Local base-pair step parameters calculated using Curves 5.1
Groove dimensions using Stoffer and Lavery de®nitions from
Curves 5.1
Crystallographic cell constants
Primary bibliographic citations
Primary bibliographic citations
Descriptor information
Crystallographic cell constants
Primary bibliographic citations
Identi®ers, descriptor, coordinate availability
Strand ID, sequence, strand length
Descriptor and experimental technique
NA Backbone Torsions
Base Pair Parameters (global)
Base Pair Step Parameters (local)
Groove Dimensions
DNA-Binding Protein
NMR Nucleic Acids
Proteins Plus
Cell Dimensions
Primary Citation
Primary Citation
Descriptor
Cell Dimensions
Primary Citation
Structure Identi®er
Sequence
Experimental Technique
Fig. 3. Examples of the different types of reports that can be generated from the NDB about torsion angles: (a) scattergram graph showing the
relationship of "(C40 ÐC30 ÐO30 ÐP) versus (C3ÐO30 ÐPÐO50 ). The two clusters, BI and BII, are labeled; (b) histogram for (O30 ÐP0 Ð
O50 ÐC50 ) for all B-DNA; (c) conformation wheel showing the torsion angles for structure BDJ025 (Grzeskowiak et al., 1991) over the average
values for all B-DNA; (d) a torsion-angle report for BDJ025.
HELEN M. BERMAN, CHRISTINE ZARDECKI AND JOHN WESTBROOK
reports produced regularly for the NDB WWW
Archives.
4.2.2. WWW interface. The WWW interface was
designed to make the query capabilities of the NDB
as widely accessible as possible. To highlight the
special features of NDB, the interface operates in two
modes. In the Quick Search/Quick Report mode,
1099
there are several items, including structure ID, author,
classi®cation and special features, which can be
limited either by entering text in a box or by selecting
an option from the pull-down menu. Any combination
of these items may be used to constrain the structure
selection. If none are used, the entire database will be
selected. After selecting `Execute Selection', the user
Fig. 4. NDB Atlas page for URX035 (Scott et al., 1995) which highlights structural information that is contained in the database and provides
images of the biological unit, asymmetric unit, and crystal packing of the structure.
1100
THE NUCLEIC ACID DATABASE
will be presented with a list of IDs and descriptors of
the structures that match the desired conditions.
Several viewing options for each structure in this list
are possible. These include retrieving the coordinate
®les in either mmCIF or PDB format, retrieving the
coordinates for the biological unit, viewing the structure with RasMol (Sayle & Milner-White, 1995), or
viewing an NDB Atlas page.
Preformatted Quick Reports can then be generated
for the structures in this results list. The user selects a
report from a list of options, and the report is created
automatically. For the structures in NDB, there are 12
different types of Quick Reports as shown in Table 3.
These reports are particularly convenient for being able
to quickly produce reports based on derived features
such as torsion angles and base morphology.
In the Full Search/Full Report mode, it is possible to
access most of the tables in the NDB and create more
complex queries. Instead of selecting from a limited
number of options, the user builds a search by selecting
the tables, and then the items, that contain the desired
features. These queries can use Boolean and logical
operators to make complex queries. An example Full
Search, ®nding transcription repressors that bind to
DNA containing the step T G, is shown in Fig. 5.
After selecting structures using Full Search, a variety
of reports can be written. The user selects the items that
are to be displayed in a report by going through the
tables that include the desired information. Multiple
reports can be generated for the same group of selected
structures; one report could list the DNA sequences, and
then another report could present the base morphology
of the bases in these sequences. Shortly, it will be
possible to draw scattergrams and histograms interactively using JAVA applets to dynamically analyze the
structural features.
Fig. 5. Example of a complex query:
selecting structures with a T G
step from the NDB and generating reports.
HELEN M. BERMAN, CHRISTINE ZARDECKI AND JOHN WESTBROOK
Another variation on this query would be to select the
protein±DNA complexes which contain a particular
sequence pattern, e.g. ACA, and then write a report
which gives the binding mode of these structures. A
report showing the binding mode demonstrates that
most of these structures are regulatory. To further re®ne
the report, the user can also include the type of regulatory protein. The report that is produced is shown in
Fig. 6.
Experimental features may be explored by
constructing a query to search for structures with cell
dimensions within a particular range. It is also possible
to search for some aspects of crystallization conditions,
although the information collected on crystallization by
the NDB is more limited than that found at the Biolo-
1101
gical Macromolecule Crystallization Database (BMCD)
(Gilliland et al., 1994).
5. NDB Archives
The NDB Archives contain a large variety of information and tables useful for researchers. These include a
variety of prepared reports that are sorted according to
structure type (Fig. 7). The dictionaries of standard
geometries of nucleic acids are here as well as parameter
®les for X-PLOR (BruÈnger, 1992). The ftp server
provides coordinates for the asymmetric unit and
Fig. 6. Reports created for protein±
DNA complexes containing the
nucleic acid sequence ACA. (a)
The top report displays the types
of regulatory proteins that bind to
the sequence ACA. (b) The
bottom report displays the nucleic
acid base morphology for the
DNA in these complexes.
1102
THE NUCLEIC ACID DATABASE
biological units in PDB and mmCIF formats, structure
factor ®les, and coordinates for nucleic acid structures
determined by NMR.
6. Other applications of NDB technology
The underlying technology of the NDB has also been
used to create relational databases for other classes of
macromolecules. The WWW interface, called Structure
Finder, is designed so that speci®c tables of information
can be turned on or off as appropriate for a particular
structural class. The decision to turn a table on or off
depends on two things: the quality of the underlying
data and the appropriateness of that table to the structure class in the database. Four databases created by the
NDB Project are described here and can be found under
Structure Finder at the NDB Biological Structure
Resource (http://ndbserver.rutgers.edu/). Tutorials for
all of the Structure Finder databases are also available at
this site.
6.1. Proteins Plus
This database is created from all the ®les in the
current PDB and is updated regularly. MAXIT (Feng et
al., 1997), a software tool developed by the NDB,
extracts data from PDB ®les which are loaded into the
database tables. A drawback of this database is that the
PDB format has changed over the years so that
abstracting information from these ®les is not entirely
reliable. To remedy this, the NDB and the Macro-
Fig. 7. Prepared Reports available
from the Archives section.
Reports are also available for ARNA with mismatches, modi®ers,
and special features; RNA±drug
complexes; t-RNA; ribozymes;
single-stranded DNA and RNA;
parallel-stranded DNA and RNA;
DNA±RNA hybrids; DNA quadruplexes; protein±DNA enzymes,
regulatory, structural, and other;
protein±RNA enzymes, regulatory and structural.
HELEN M. BERMAN, CHRISTINE ZARDECKI AND JOHN WESTBROOK
molecular Structure Database (MSD) group at EBI are
working to put the PDB ®les into a uniform format and
add any missing data items. In the cases in which ®les
have been recurated, the newly processed ®le is available from Proteins Plus. Once all the ®les have been
remediated, many additional tables will be available for
searching.
The Proteins Plus database can be searched using
Quick Search/Quick Reports and Full Search/Full
Reports, which are used in the same way as for the NDB.
An example of a Proteins Plus query and report session
might be to search for all myoglobin structures and then
to create a report of all crystal data or another which
lists the positions of the helices (Fig. 8).
1103
7. Summary
The NDB Project has evolved over the years. The
original NDB contained fewer than 100 crystal structures of nucleic acids; there are now over 700. In addition, the project has created a suite of speciality
databases and technologies that will allow for the
evolution of these databases. The strength of the search
engines developed by this project is that they allow for
rapid selection of structures by a wide variety of criteria.
Once selected, the coordinates of these structures, along
with the tabular and graphical report capabilities of the
NDB, can be used to understand a large number of the
characteristics of these structures. The curated and
reliable ®les that are provided by the NDB can also be
used by other independent programs.
6.2. DNA binding proteins
All proteins which bind to DNA have been fully
curated and annotated and placed into a database. The
database includes protein±DNA complexes as well as
proteins that bind to DNA but do not have DNA in the
crystal. The functions of these proteins are available as
both search targets and report content.
6.3. Nucleic acid NMR
This database contains all NMR structures that
contain nucleic acids. This database can be searched
using Quick Search/Quick Report. Further curation of
these structures is a future project.
8. Access
The home for the Nucleic Acid Database can be found
on the NDB Biological Structure Resource Home page
(http://ndbserver.rutgers.edu/). On this page are pointers to the NDB and Structure Finder, as well as to aÁ la
mode (Clowney & Westbrook, 1997), which is a database
of ligands and monomer units, and to the mmCIF WWW
site. In addition to backup mirror sites at Rutgers
University, the NDB is mirrored at the European
Bioinformatics Institute (Europe), NIBH-AIST (Japan),
and San Diego Supercomputer Center (US), with
additional public mirrors currently in development.
These mirrors are kept synchronous by using software
tools developed by the project.
Fig. 8. An example of a Proteins Plus
query and report.
1104
THE NUCLEIC ACID DATABASE
This work has been funded by the National Science
Foundation (BIR 95 10703).
References
Allen, F. H., Bellard, S., Brice, M. D., Cartright, B. A.,
Doubleday, A., Higgs, H., Hummelink, T., HummelinkPeters, B. G., Kennard, O., Motherwell, W. D. S., Rodgers, J.
R. & Watson, D. G. (1979). Acta Cryst. B35, 2331±2339.
Berman, H. M., Olson, W. K., Beveridge, D. L., Westbrook, J.,
Gelbin, A., Demeny, T., Hsieh, S.-H., Srinivasan, A. R. &
Schneider, B. (1992). Biophys. J. 63, 751±759.
Bernstein, F. C., Koetzle, T. F., Williams, G. J. B., Meyer, E. F.,
Brice, M. D., Rodgers, J. R., Kennard, O., Shimanouchi, T. &
Tasumi, M. (1977). J. Mol. Biol. 112, 535±542.
Bourne, P., Berman, H. M., Watenpaugh, K., Westbrook, J. D.
& Fitzgerald, P. M. D. (1997). Methods Enzymol. 277, 571±
590.
BruÈnger, A. T. (1992). X-PLOR, Version 3.1, A System for
X-ray Crystallography and NMR, Yale University Press,
New Haven, CT, USA.
Clowney, L., Jain, S. C., Srinivasan, A. R., Westbrook, J., Olson,
W. K. & Berman, H. M. (1996). J. Am. Chem. Soc. 118, 509±
518.
Clowney, L. & Westbrook, J. D. (1997). aÁ la mode: A Ligand
and Monomer Object Data Environment, NDB-241, Rutgers
University, New Brunswick, NJ, USA.
Feng, Z., Hsieh, S.-H., Gelbin, A. & Westbrook, J. (1997).
MAXIT: Macromolecular Exchange and Input Tool, NDB220, Rutgers University, New Brunswick, NJ, USA.
Gelbin, A., Schneider, B., Clowney, L., Hsieh, S.-H., Olson, W.
K. & Berman, H. M. (1996). J. Am. Chem. Soc. 118,
519±528.
Gilliland, G. L., Tung, M., Blakeslee, D. M. & Ladner, J. E.
(1994). Acta Cryst. D50, 408±413.
Grzeskowiak, K., Yanagi, K., PriveÂ, G. G. & Dickerson, R. E.
(1991). J. Biol. Chem. 266, 8861±8883.
Lavery, R. & Sklenar, H. (1988). J. Biomol. Struct. Dyn. 6, 63±
91.
Parkinson, G., Vojtechovsky, J., Clowney, L., BruÈnger, A. T. &
Berman, H. M. (1996). Acta Cryst. D52, 57±64.
Sayle, R. & Milner-White, J. E. (1995). Trends Biochem. Sci. 20,
374.
Schneider, B., Neidle, S. & Berman, H. M. (1997). Biopolymers,
42, 113±124.
Scott, W. G., Finch, J. T. & Klug, A. (1995). Cell, 81, 991±1002.
Watson, J. D. & Crick, F. H. C. (1953). Nature (London), 171,
737±738.